CN110121329A

CN110121329A - Local skin blast additive and composition with amino acid and PPAR activation fatty acid

Info

Publication number: CN110121329A
Application number: CN201780079471.8A
Authority: CN
Inventors: A·达莫达兰; A·库马里; 黄楠; 宓婷艳; B·哈里奇安; J·G·罗萨
Original assignee: 荷兰联合利华有限公司
Current assignee: Unilever IP Holdings BV
Priority date: 2016-12-21
Filing date: 2017-12-18
Publication date: 2019-08-13
Anticipated expiration: 2037-12-18
Also published as: US20200009034A1; CA3046137A1; WO2018113636A1; EP3558245A1; CN110121329B; EP3558245B1; EP3558245A4

Abstract

Skin lightening additive and personal care composition containing amino acid and PPAR activation fatty acid cpds.The composition can be used for obtaining even skin tone and reduce pigmentation, senile plaque and discoloration.

Description

Local skin blast additive and group with amino acid and PPAR activation fatty acid Close object

Technical field

Topical composition the present invention relates to skin lightening additive and comprising the additive.

Background technique

Many consumers are concerned about their skin characteristic.For example, consumer is concerned about the pigmentation level of their skins, sparrow Spot and/or senile plaque.Other consumers wish to reduce dimmed by being exposed to sun-induced skin.In order to meet the need of consumer It asks, many trials has been carried out to develop the product for improving skin characteristic.However, the product developed so far often tends to have There are low effect, undesirable side effect or both to have both at the same time.The more and more interesting exploitation of people adds comprising new skin lightening Add the cosmetic composition of agent.

The tripeptides that glutathione (GSH) is made of glutamate, cysteine and glycine.It is present in all lactations In animal tissue.It is the primary anti-oxidant in living body: it protects cells from oxidation by quenching activity oxygen species.Carefully The damage of born of the same parents' content increased GSH protection cells from oxidative, toxic chemical and radiation (Meister, J.Biol.Chem.263: 205—217,1988；Meister,Science 200:471—477,1985).Although all areas of body be all as This, but this is especially important in skin, and skin is greatly exposed to the destructiveness of radiation, particularly UV radiation and environmental contaminants Effect.The reduction of the intracellular concentration of skin GSH-PX activity and cellular damage, inflammation, skin are dimmed, change colour, by being exposed to purple The correlations such as spot caused by external radiation or freckle, physiological aging.

A kind of realization skin lightening and/or confrontation skin is dimmed, discoloration or pigmented logical method seem It is that the GSH of exogenous source (such as by intake or local delivery) is provided to cell.In fact, GSH has been used as skin sometimes The sale of skin blast ingredient.Unfortunately, GSH is not bioavailable in exogenous application, i.e., in extracellular positioning, GSH is broken down into it and forms amino acid (glutamate, cysteine and glycine), cellular uptake and conjunction for GSH tripeptides At.Therefore, GSH is not directly transferred into cell, therefore itself not will lead to the intracellular of GSH and increased or associated appoint What benefit.Cysteine is one of GSH amino acid, can increase the cell content of GSH, but the sulfydryl of cysteine exposure makes Its is unstable and has reactivity, and also causes strong undesirable smell.Different from cysteine, cystine can pacify Full application；Cystine is transported in cell and is converted into cysteine in the cell, and then cysteine can be used for into the cell The generation of GSH.

The topical composition containing various amino acid and other skin care active objects has been described, see, for example, The US7300649 of Tanojo, Laboratoire Filorga product, Schlachter WO 00/03689, Ermolin etc. US 8,361,446, the Hermann's of US4,707,354, Muller of US2011183040, Garlen etc. etc. etc. US8241681.The composition for enhancing glutathion inside cell generation has been described.See, for example, the U.S. of Chiba etc. Patent 7,740,831, Crum etc. (USRE37934, USRE42645, WO2016/033183 and US20050271726)； The United States Patent (USP) 6,149,925 of Mammone and the US 20060063718 of Perricone.

Cystine is typically derived from diet.It is challenging however, delivering cystine from topical composition, because Its solubility in neutral pH range in biologically acceptable carrier is extremely low, and the pH range is needed for part applies PH range.The solubility of cystine in water is 0.112mg/ml at 25 DEG C；Cystine is more soluble in pH and is higher than less than 2 or pH In 8 aqueous solution.

The present invention is based partially on it has surprisingly been found that i.e. comprising the modified of cystine, glutamate and glycine What the combination of GSH module (block) ispol and PPAR activation fatty acid realized skin lightening cooperates with increase, therefore The shortcomings that counteracting the low solubility of cystine.

Summary of the invention

In one embodiment, personal care composition according to the present invention includes:

In one embodiment, topical cosmetic dermal compositions are leave-on compositions, and especially leave is non-solid Body composition.

In one embodiment, the present invention provides the method for improving skin appearance comprising applies the office to skin Portion's cosmetic skin composition.

In one embodiment, the present invention provides the method for improving skin appearance comprising applies personal shield to skin Manage composition.

In one embodiment, the present invention provides obtain even skin tone and reduce pigmentation, senile plaque and discoloration Method comprising apply the composition to skin.

Composition of the invention is by even skin tone, skin lightening, counteracting by being exposed to UV light/daylight or environmental contaminants Caused by discoloration, pigmentation, senile plaque and skin it is dimmed, improve the skin due to caused by aging at any time or light aging Appearance.The preferred method for obtaining the benefit of composition is applied by regular/long-term part of composition, to prevent even day It often is exposed to the development for the skin injury that UV light may cause.

The detailed description of invention

In entire disclosure and claims, unless the context clearly determines otherwise, otherwise following term uses this Civilized really relevant meaning.

It phrase " in one embodiment " as used herein and is not necessarily meant to refer to " in some embodiments " identical Embodiment, although it can refer to identical embodiment.In addition, phrase " in another embodiment " as used herein " in some of the other embodiments " is not necessarily meant to refer to different embodiments, although it can refer to different embodiments. Therefore, as described below, without departing from the scope or spirit of the invention, various realities of the invention can easily be combined Apply scheme.In addition, with regard to each embodiment that various embodiments of the present invention provide be intended to be illustrative and not restrictive.

In addition in embodiment or it is otherwise explicitly indicated in the case where other than, the amount or anti-of material is indicated in this specification All numbers of condition, the physical property of material and/or purposes are answered to should be understood as being modified by word " about ".Unless otherwise saying Bright, otherwise all amounts are with the poidometer of final composition.The disclosure found herein should be considered covering All embodiments found in mutual claim are subordinated to multiple, without considering in no multiple subordinate or redundancy In the case where it may be found that claim the fact.It is any specific more highly concentrated in any range of prescribed concentration or amount Degree can be associated with any specific low concentration or amount.

" comprising " is intended to mean "comprising", but be not necessarily " by ... form " or " by ... constitute ".In other words, institute The step of column or option need not be exhaustive.

" skin " is intended to include on face, neck, chest, back, arm (including oxter), hand, leg, buttocks and scalp Skin.

" leave-on composition " refers to following composition, is applied to skin, with after application immediately or a few minutes just wash The skin cleaning going or wash off washes off type or rinse-off compositions are compared, and whithin a period of time, does not beat in a few houres especially Calculation is washed away or is washed off.

It is " non-solid " for the composition mean the composition have 1Pas to 500Pas, preferably 2Pas extremely Within the scope of 100Pas, more preferable 3Pas to 50Pas measurable viscosity (such as can with Brookfield viscometer DV-I+ (20RPM, RV6, 30 seconds, 20 DEG C) measurement).

" personal care composition " refers to application as human body for improving appearance, sun-proof, cleaning, smell control, moisturizing Or general beautiful any product.The non-limiting example of personal care composition include skin care milk, creme (cream), gel, Emulsion (lotion), facial mask, stylus, shampoo, conditioner, bath gels, toilet bars, antiperspirant, deodorant, shaving cream, Depilatory agent, lipstick, foundation cream, mascara, Sunless tanning agent and sunscreen.

" skin cosmetic composition ", which refers to, is applied to human body for improving appearance, sun-proof, reduction wrinkled appearance or other Light aging sign, smell control, skin lightening, even skin tone or general aesthetics any product.Topical cosmetic skin group The non-limiting example for closing object includes skin care milk, creme, facial mask, gel, stylus, antiperspirant, deodorant, lipstick, foundation cream, eyelashes Cream, liquid or gel shower cream, soap bar, Sunless tanning agent and sunscreen.

The non-solid skin cosmetic composition of the preferred leave of the personal care composition of this technology, because due to cystine Solubility is low and most challenging in terms of mixing cystine.

Modified glutathione (" GSH ") amino acid

GSH ispol according to the present invention includes amino acid (glutamate, cystine and glycine).

Comprising amino acid in the compositions of the present invention with the presence of L stereoisomer, because this is to find in nature Most abundant and natural isomeric form.Due to the structure of the naturally occurring protein found in application on human skin, hair and nail Modeling block is the amino acid with L isomeric form, it is therefore expected that L stereoisomer contained in personal care product of the invention Amino acid can have the bigger interaction with these protein, in itself inherently compared with D stereoisomeric forms in any ratio More bio-compatible.In addition, the commodity production and supply of L stereo isomer amino acids are significant compared with D stereoisomer form It is higher.Finally, compared with D stereo isomer amino acids, the production of L stereo isomer amino acids get up it is also more cost effective, more It is sustainable, more ecological close friend, and can be obtained with lower cost.

Comprising any amino acid in the present invention can in the form of salt, ester or its salt, and in this specification it is used Term " cystine ", " glutamic acid Yanyuan " and " glycine " also cover the salt of salt, ester and such ester.Salt, ester and such ester Salt is not particularly limited, as long as it is acceptable part application.For example, can be mentioned that and inorganic acid or organic acid or yin The salt of ionic surfactant.As inorganic acid, can be mentioned that such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, as straight Chain, branch or ring-type, saturation or unsaturation, it is unsubstituted or through hetero atom replace C1-C18 organic acid, can be mentioned that such as formic acid, Acetic acid, trifluoroacetic acid, propionic acid, lactic acid, tartaric acid, oxalic acid, fumaric acid, succinic acid, maleic acid, citric acid, malonic acid, methylsulphur Acid, stearic acid, oleic acid, 12- hydroxy stearic acid, ricinoleic acid etc..

As the salt with alkali, can be mentioned that such as alkali metal salt as sodium salt, sylvite, alkali salt such as calcium salt, magnesium salts etc. Deng.

The ester of amino acid is usually C₁-C₈Ester or its salt, or be selectively C₁-C₅Ester, or be selectively C₁-C₃Ester. Such ester can be linear chain or branched chain or cricoid.The ester of especially cystine is beneficial, because compared with cystine, they Solubility increase.The methyl esters and ethyl ester or its salt of cystine are most preferred, because they have the production for promoting glutathione The effect of raw and offer antioxidant activity.When using the salt of ester, identical salt listed above is suitable.

Presence-glutamine, glutamic acid and/or burnt paddy ammonia can be used in the form of its functional equivalent in glutamic acid Yanyuan Acid and/or their ester or salt.It is preferred that pyroglutamic acid (and/or its salt), because it is more more stable than glutamine or glutamic acid.? In one embodiment, skin lightening additive includes cystine and pyroglutamic acid and glycine (and/or its salt).

PPAR activates fatty acid

The fatty acid for being suitable as skin lightening additive of the invention includes but is not limited to: 12- hydroxy stearic acid, conjugation Linoleic acid, ricinoleic acid, petroselic acid, cis- -9- anti-form-1 1- conjugated linoleic acid, cis- -12 conjugated linoleic acid of anti-form-1 0-, 7- Trans- octadecanoid acid, cis--parinaric acid, docosahexaenoic acid, two dodecahexaene of cis- -4,7,10,13,16,19- Acid, ricinelaidic acid (ricinolaidic acid), parinaric acid (stearidonic acid), octatecatrienoic acid (columbinic acid), anti-linolenic acid, vaccenic acid, eicosapentaenoic acid, Pinolenic acid (pinolenic acid) and it Mixture.It has been found that skin lightening collaboration increases by means of including that amino acid as described herein and PPAR activate fatty acid The shortcomings that adding, therefore overcoming cystine limited solubility.

In one embodiment, composition of the invention is the personal nursing that pH is 3.5 to 8.5, pH in particular 5 to 8 Topical creams, emulsion, gel, creme or toilet cream form leave inventive non-solid compositions, it includes cystines, glutamate The skin lightening additive of (especially pyroglutamic acid or its salt, such as sodium pyroglutamate), glycine and 12- hydroxy stearic acid.

In one embodiment, composition of the invention is the personal nursing that pH is 3.5 to 8.5, pH in particular 5 to 8 Topical creams, emulsion, gel, creme or toilet cream form leave inventive non-solid compositions, it includes cystines, glutamate The skin lightening additive of (especially pyroglutamic acid or its salt, such as sodium pyroglutamate), glycine and conjugated linoleic acid.

In one embodiment, composition of the invention is the personal nursing that pH is 3.5 to 8.5, pH in particular 5 to 8 Topical creams, emulsion, gel, creme or toilet cream form leave inventive non-solid compositions, it includes cystines, glutamate The skin lightening additive of (especially pyroglutamic acid or its salt, such as sodium pyroglutamate), glycine and petroselic acid.

In one embodiment, composition of the invention is the personal nursing that pH is 3.5 to 8.5, pH in particular 5 to 8 Topical creams, emulsion, gel, creme or toilet cream form leave inventive non-solid compositions, it includes cystines, glutamate The skin lightening additive of (especially pyroglutamic acid or its salt, such as sodium pyroglutamate), glycine and ricinoleic acid.

Amount

In one embodiment, cystine with 0.001% to 2% or selectively 0.005% to 1% or 0.008% to 0.5% or selectively 0.008% to 0.4% amount by comprising.In one embodiment, glutamic acid Yanyuan (preferably pyroglutamic acid salt) is with 0.01% to 10% or selectively 0.01% to 5% or 0.05% to 1% or selectively 0.05% to 0.5% amount by comprising.In one embodiment, glycine source is with 0.01% to 10% or selectively 0.01% to 5% or 0.05% to 1% or selectively 0.05% to 0.5% amount by comprising.In one embodiment, PPAR activates fatty acid with 0.01% to 5% or selectively 0.05% to 5% or 0.1% to 5% or selectively 0.1% to 3% amount by comprising.

In one embodiment, the total weight of amino acid is at least 10 times of the weight of PPAR activation fatty acid.One In a embodiment, the weight ratio of total amino acid and PPAR activation fatty acid is in the range of 10:1 to 20:1.Selectively, always The weight ratio of amino acid and resorcinol is in the range of 10:1 to 15:1.

Carrier

Composition of the invention also includes acceptable carrier on cosmetics.The amount of carrier can 1% to 99.9%, preferably 70% to 95%, best 80% to 90% range.Useful carrier have water, emollient, fatty acid, fatty alcohol, thickener and Their combination.Carrier can be aqueous, anhydrous or lotion.Preferably, the composition is aqueous, especially oil packet The water and fat liquor (water and oil emulsions) or W/O/W or Water-In-Oil packet oil of water or oil-in-water type become The multiple emulsion of type.When it is present, the amount of water can 5 weight % to 95 weight %, preferably from about 20 weight % to about 70 weight %, The range of best 35 weight % to 60 weight %.

Emollient materials can act on as carrier acceptable on cosmetics.These can in silicone oil, natural or synthetic ester, The form of hydrocarbon, pure and mild fatty acid.The amount of emollient can be with the poidometer 0.1 to 95% of composition, preferably 1% to 50% Arbitrary value in range.

Silicone oil can be divided into volatility and non-volatile type.Term " volatility " as used herein refers in environment temperature Degree is lower to have those of measurable vapour pressure material.Volatile silicone oils are preferably selected from containing 3 to 9, preferably 5 to 6 silicon originals The ring-type (Cyclomethicone) or linear polydimethyl siloxane of son.It includes poly- for can be used as the non-volatile silicone oil of emollient materials Alkylsiloxane, Polyalkylaryl siloxane and polyether siloxane copolymer.It can be substantially non-volatile in this article Polyalkylsiloxane includes having 5 × 10 for example at 25 DEG C^-6To 0.1m²The dimethyl silicone polymer of the viscosity of/s.It can be used for Preferred non-volatile emollients in this composition, which are included at 25 DEG C, has 1 × 10^-5To about 4 × 10^-4m²The viscosity of/s Dimethyl silicone polymer.

Another kind of nonvolatile silicone is emulsification and non-emulsified silicone elastomer.The representative of the category is as Dow Dimethicone/second that Corning 9040, General Electric SFE 839 and Shin-Etsu KSG-18 are obtained Alkenyl dimethicone cross-linked polymer.Silicone wax also can be used, such as Silwax WS-L (the dimethicone copolyol moon Cinnamic acid ester (Dimethicone Copolyol Laurate)).

In ester emollient, have:

A) Arrcostab of the saturated fatty acid with 10 to 24 carbon atoms.The example includes neopentanoic acid Shan Yu ester, different nonyl The different nonyl ester of acid, isopropyl myristate and octyl stearate.

B) ether-ether, such as the aliphatic ester of ethoxylation saturated fatty alcohol.

C) polyol ester.Ethylene glycol fatty acid ester and di-fatty acid esters, diglycol monotertiary aliphatic ester and two are sweet Alcohol di fatty acid ester, polyethylene glycol (200-6000) mono fatty acid ester and polyethylene glycol (200-6000) di fatty acid ester, the third two Alcohol mono fatty acid ester and Propylene glycol di-fatty acid ester, 2000 monostearate of polypropylene glycol, ethoxylated propylene glycols monostearate Ester, mono fatty acid glyceride and the poly- fatty ester of difatty acid glyceride, polyglycereol, ethoxylation glycerin monostearate, 1,3- Butanediol monostearate, 1,3 butylene glycol distearate, polyoxyethylene polyol fatty acid esters, sorbitan fatty Acid esters and polyoxyethylene sorbitan aliphatic ester are satisfactory polyol esters.Be especially useful that pentaerythrite, Trimethylolpropane and C₁-C₃₀The neopentyl glycol ester of alcohol.

D) wax ester, such as beeswax, spermaceti and San Shan Yu essence wax (tribehenin wax).

E) sugar ester of fatty acid, such as the poly- behenic acid ester of sucrose and the poly- cottonseed acid esters of sucrose.

Natural ester emollients are based primarily upon monoglyceride, diglyceride and triglycerides.Representative glyceride include to Day seed oil of sunflower, cottonseed oil, borage oil, Common Borage seed oil, evening primrose oil, castor oil and rilanit special, rice bran oil, soybean Oil, olive oil, safflower oil, sher butter, jojoba oil and their combination.The emollient of animal origin is by lanolin oil and sheep Hair rouge derivative represents.The amount of natural esters can be with the range of the poidometer 0.1% to 20% of the composition.

Hydrocarbon as acceptable carrier on suitable cosmetics includes vaseline, mineral oil, C₁₁-C₁₃Isoparaffin, poly- fourth Alkene especially can be used as the isohexadecane that Permethyl 101A is commercially available from Presperse Inc..

Fatty acid with 10 to 30 carbon atoms can also be suitable as acceptable carrier on cosmetics.The reality of the category Example is n-nonanoic acid, lauric acid, myristic acid, palmitinic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, hydroxy stearic acid He behenic acid and their mixture.

Fatty alcohol with 10 to 30 carbon atoms is acceptable carrier on the cosmetics of another useful classification.The category Example be stearyl alcohol, laruyl alcohol, myristyl alcohol, oleyl alcohol and cetanol and their mixture.

Thickener or rheology modifier can be used as one of acceptable carrier on the cosmetics of composition according to the present invention Part.Typical thickener includes acrylate (such as the Carbopol of crosslinking), the acrylate (example of hydrophobically modified Such as Carbopol), polyacrylamide (such as Sepigel), acryloyl methyl propane sulfonic acid/salt polymer and Copolymer (such as AristoflexWith), cellulose derivative and natural gum.Spread out in useful cellulose Biology, in have sodium carboxymethylcellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose And hydroxymethyl cellulose.Suitable for natural gum of the invention include guar gum, xanthan gum, sclerotium, carrageenan, pectin and these The combination of glue.Inorganic matter also be used as thickener, especially clay such as bentonite and hectorite, pyrolytic silicon dioxide, talcum, Calcium carbonate and silicate such as aluminium-magnesium silicateThe amount of thickener can be 0.0001% to 10%, usual 0.001% To 1% or 0.01% to 0.5% range.

Particularly with the product for being intended to be applied to face, the emollient for improving organoleptic properties may be preferably used for, and it is selected From below group: -14 butyl ether of polypropylene glycol (also referred to as Tegosoft PBE) or PPG15 stearyl ether such as Tegosoft E, its Its oil such as ester especially isopropyl myristate, isopropyl palmitate, other oil may include castor oil and its derivative.

The wetting agent of polyhydric alcohol-type can be used as acceptable carrier on cosmetics.Typical polyalcohol includes glycerol, gathers Aklylene glycol and they pure and mild derivative of more preferable alkylene polyol, including it is propylene glycol, dipropyl glycol, polypropylene glycol, poly- Ethylene glycol and its derivative, D-sorbite, hydroxypropyl sorbitol, hexylene glycol, 1,3 butylene glycol, isoprene, 1,2,6- oneself Triol, ethoxylated glycerol, propoxylated glycerol and their mixture.The poidometer that the amount of wetting agent can be with composition Arbitrary value in the range of 0.5% to 50% and preferably 1% to 15%.

It may include skin moisturizer, such as hyaluronic acid and/or its precursor N-acetyl-glucosamine.N-acetyl-glucosamine can be It finds, and can be commercially available from Maypro Industries, Inc (New York) in Shark cartilage or mushroom.Other preferred guarantors Humectant includes three (C of hydroxypropyl₁-C₃Alkyl) ammonium salt.These salt can be obtained with various synthesis technologies, most particularly by hydrolysis chlorine Three (C of hydroxypropyl₁-C₃Alkyl) ammonium salt acquisition.Most preferred substance is 1,2- dihydroxypropyl trimethyl ammonium chloride, wherein C₁-C₃Alkane Base is methyl.The amount of the salt can with the poidometer 0.2% to 30% of topical composition and preferably 0.5% to 20%, it is best 1% to 12% range, including all ranges included in it.

C on usual quaternized ammonium₁-C₃Alkyl component can be methyl, ethyl, n-propyl, isopropyl or ethoxy and Their mixture.Particularly preferably it is known as the trimethyl ammonium group of " trimethylammonium (trimonium) " group by INCI nomenclature. Any anion is used equally in the quaternary ammonium salt.Anion can be organic or inorganic, and condition is that the material is makeup It is acceptable on product.Typical inorganic anion is halogen ion, sulfate radical, phosphate radical, nitrate anion and borate.Most preferably halogen from Son, especially chloride ion.Organic anionic counter ions include methyl-sulfuric acid root, toluoyl sulfate, acetate, citrate, Tartrate anion, lactate, glucose acid group and benzene sulfonic acid root.

It include the urea replaced especially in combination with other still preferred moisturizer workable for above-mentioned ammonium salt, such as methylolurea, hydroxyl Ethyl carbamide, hydroxypropyl urea；Bis- (methylol) ureas；Bis- (ethoxy) ureas；Bis- (hydroxypropyl) ureas；N, N '-dimethylol urea；N,N'- Dihydroxy ethyl urea；N, N '-dihydroxypropyl urea；N, N, N '-trihydroxyethyl urea；Four (methylol) ureas；Four (ethoxy) ureas；Four (hydroxyls Propyl) urea；N- methyl, N '-ethoxy urea；N- ethyl-N '-ethoxy urea；N- hydroxypropyl-N '-ethoxy urea and N, N ' diformazan Base-N- ethoxy urea.When term hydroxypropyl occurs, the meaning is to 3- hydroxy-n-propyl, 2- hydroxy-n-propyl, 3- hydroxyl isopropyl Base or 2- hydroxyisopropyl are general.Most preferably ethoxy urea.The latter can be using trade mark Hydrovance as 50% water Property liquid is obtained from the National Starch&Chemical Division of ICI.In topical composition for use in the present invention Substituted urea range of the amount 0.01% to 20% or 0.5% to 15% or 2% to 10%.When use ammonium salt and/or substitution Urea when, in embodiment most particularly preferably, use at least 0.01% to 25% or 0.2% to 20% or 1% to 15% Wetting agent, such as glycerol.It include vaseline and/or various aquaporins operation active matter with other moisturizer in this article And/or oat kernel powder.

The pH of composition

In one embodiment, the pH of personal care composition is 3.5 to 8.5.In some embodiments, personal shield The pH for managing composition is pH 3.5 to pH 8.In some embodiments, the pH of personal care composition is pH 5 to pH 7.8. In some embodiments, the pH of personal care composition is 5 to 7.5.

Preferred optional member

In some embodiments, personal care composition of the invention and especially leave skin cosmetic composition Contain sun-screening agent.These are usually the combination of Orangic sunscreen and inorganic sunscreen.It is especially important that UV-A and UV-B to be included Radiate sun-screening agent.

UV-B sunblock lotion can be selected from the classification of cinnamic acid, salicylic acid, diphenylacrylate or derivatives thereof.UV-B sunblock lotion It may include one of following or a variety of: octyl salicylate, 2 hydroxybenzoic acid 3,3,5- 3-methyl cyclohexanol ester, salicylic acid ethyl Own ester, 2- cyano -3,3- diphenyl -2- 2-EHA or Ethylhexyl Methoxycinnamate (also referred to as first Oxygroup cinnamic acid monooctyl ester or " OMC ").Such UV-B sunblock lotion is usually available commercially, such as Octisalate^TM(bigcatkin willow is misery Ester), Homosalate^TM(2 hydroxybenzoic acid 3,3,5- 3-methyl cyclohexanol ester), NeoHeliopan^TMA series of (organic UV mistakes Filtering agent, including OMC (Neo Heliopan AV^TM) and ethylhexyl salicylate (Neo Heliopan OS^TM))、 Octocrylene^TMWith Milestab 3039^TM(2- cyano -3,3- diphenyl -2- 2-EHA) or Parsol MCX^TM(Ethylhexyl Methoxycinnamate).The amount of UV-B sunblock lotion can be 0.1 weight % in personal care composition To 20 weight % or 0.2 weight % to 10 weight % or 0.5 weight % to 7 weight % or 2 weight % to 6 weight %.

Personal care composition can further include water-soluble UV-B sun-screening agent.Water-soluble UV-B sun-screening agent may also include benzene Base benzimidazole sulfonic acid (also referred to as ensulizole (ensulizole)), 4-aminobenzoic acid (also referred to as p-aminobenzoic acid or " PABA ") or both.

The personal care composition of any one the embodiment above can further include 0.1 weight % to 10 weight %'s UV-A sunblock lotion.UV-A sunblock lotion may include below one or more: 4- tert-butyl -4'- methoxy dibenzoylmethane (" Avobenzone "), 2- methyldiphenyl formyl methylmethane, 4- methyl-dibenzoyl base-ethane, 4- isopropyldibenzoylmethane- Methane, 4- butyldibenzoylmethane, 2,4- dimethyldibenzoylmethane, 2,5- dimethyl dibenzoyl first Alkane, 4,4'- diisopropyl dibenzoyl methane, 2- methyl -5- isopropyl -4'- methoxy-dibenzoylmethane, 2- first Base -5- tert-butyl -4'- methoxy-dibenzoylmethane, 2,4- dimethyl -4'- methoxy dibenzoylmethane, 2,6- Dimethyl -4- tert-butyl -4'- methoxy-dibenzoylmethane, diethylamino-hydroxybenzoyl-hexyl-benzoate, according to camphane Relax (ecamsule) or methyl anthranilate.The amount of UV-A sunblock lotion can be 0.5 weight % in personal care composition To 7 weight % or 1 weight % to 5 weight %.

It include commercially available from BASF Corporation suitable for the other suitable sunblock lotion personal care composition Those of obtain: Uvinul T-150 (Uvinul T 150；UV-B sunblock lotion), Uvinul A Plus (lignocaine hydroxyl Benzoyl hexyl-benzoate；UV-A sunblock lotion), Tinosorb S (bis-ethylhexyloxyphenol methoxyphenyl triazine；UV-A and UV-B sunblock lotion), Tinosorb M (di-2-ethylhexylphosphine oxide benzotriazole base tetramethyl butyl phenol；UV-A and UV-B sunblock lotion).Phenyl Bisbenzimidazole tetrasulfonic acid ester disodium (Bisdisulizone disodium) can also reside in personal care composition.

The particularly preferred combination of UV-A sunblock lotion and UV-B sunblock lotion is Avobenzone and 4- methoxy cinnamic acid 2- second The own ester of base.

In some embodiments, sun-screening agent is inorganic sunscreen.Nothing suitable for skin care compositions and methods of the present invention The example of machine sun-screening agent includes but is not limited to microfine titanium dioxide, zinc oxide, polyethylene and various other polymer.Term is " micro- Carefully " mean particle of the average-size in 10-200 nanometers or 20-100 nanometer range.When being present according to the present invention one When in the skin nursing formulation of a little embodiments, the amount of sun-screening agent can 0.1% to 30% or 2% to 20% or 4% to 10% range.

Although may include selenium source, selenium source is preferably avoided in Topical skin care composition of the invention, because at certain It is considered as skin sensitization agent under a little supervision governments form.Therefore, the amount of selenium is 0 to maximum 0.1% in this composition, or at most 0.05%, most preferably it is no more than 0.01%.

Other than the skin lightening additive being contained herein, composition of the invention preferably also includes skin lightening Object is closed, to obtain optimal skin lightening performance with optimum cost.Illustrative substance is intacellin, lactic acid, isophthalic Diphenol (resorcinol that 4- replaces, the disubstituted resorcinol of 2,5-, the disubstituted resorcinol of 4,5- and 4,6 disubstituted Resorcinol, especially 4- hexyl resorcin, cresorcinol, 4- butyl resorcinol, 4- isopropyl meta-dihydroxybenzene, Symwhite-337), niacinamide and derivative, arbutin, kojic acid, ferulic acid, quinhydrones, resorcinol derivatives (including two Substituted resorcinol) and their combination.In one embodiment, such Skin lightening compounds are that tyrosinase inhibits Agent is most preferably selected from by the compound of kojic acid, quinhydrones and other (non-4 resorcinols replaced).There are also by formula HOOC- (CxHy) dicarboxylic acids that-COOH (wherein x=4 to 20 and y=6 to 40) is indicated, such as azelaic acid, decanedioic acid, oxalic acid, amber Acid, fumaric acid, octadecene diacid (such as Arlatone DC) or their salt or their mixture, most preferably fumaric acid or Its salt, especially disodium salt.It has been found that especially for skin lightening formulation, particularly preferred 12HSA and fumaric acid or its salt Combination.The amount of these reagents can be with the poidometer of the composition about 0.1% to about 10%, preferably from about 0.5% to about 2% Range.It is preferred that it is niacinamide or resorcinol, especially 4- that skin lightening according to the present invention, which is total to activating agent (coactive), Alkyl-resorcin.

Another preferred component of the present composition is retinoids (retinoid).As used herein, " retinoids " All natural and/or synthesis of the bioactivity with vitamin A in skin including vitamin A or retinol-like compounds The geometric isomer and stereoisomer of analog and these compounds.The preferred retinol of retinoids, retinol ester (example Such as, the C of retinol₂-C₂₂Arrcostab, including retinyl palmitate, retinoic acid ester, Vitamin A propionate), retinene and/or view Yellow acid (including all-trans retinoic acid and/or 13CRA), the retinoids more preferably in addition to retinoic acid.These are changed It is well-known in the art for closing object, and can be commercially available from many sources, such as Sigma Chemical Company (St.Louis, Mo.) and Boerhinger Mannheim (Indianapolis, Ind.).It can be regarded with other classes in this article Flavol is described in U.S. Patent No. 4,677,120 for giving Parish etc. on June 30th, 1987；On December 5th, 1989 is given The U.S. Patent No. of Parish etc. 4,885,311；September in 1991 gives the U.S. Patent No. 5,049 of Purcell etc. on the 17th, No. 584；On June 23rd, 1992 gives U.S. Patent No. 5,124,356 of Purcell etc.；It was given on September 22nd, 1992 The United States Patent (USP) of Purcell etc. is issued again in No. 34,075.Other suitable retinoids are retinoic acid Renascins (depending on Huang The Renascin of sour (trans- or cis-)), Adapalene (adapalene) { 6- [3- (1- adamantyl) -4- methoxybenzene Base] -2- naphthoic acid }) and tazarotene (tazarotene) (6- [2- (4,4- dimethylthiochroman -6- base)-acetylene Base] ethyl nicotinate).Preferred retinoids are retinol, retinyl palmitate, retinoic acid ester, Vitamin A propionate, retinene And their combination.Retinoids be preferably generally it is pure, it is more preferably substantially pure.Composition of the invention can contain The retinoids safely and effectively measured so that resulting composition for adjust collenchyme illness, preferably for adjust skin in The visible and/or discontinuity that can touch, more preferably for adjusting signs of skin aging, even more preferably for adjusting and skin Discontinuity that is visible and/or can touching in the relevant skin texture of aging is safely and effectively.The composition preferably comprises 0.005% to 2% or 0.01% to 2% retinoids.Retinol preferably with or 0.01% to 0.15% amount use；Depending on Huang Alcohol ester is preferably used with the amount of 0.01% to 2% (such as 1%)；Retinoic acid is preferably used with 0.01% to 0.25% amount；And And retinoic acid Renascin, Adapalene and tazarotene are preferably used with 0.01% to 2% amount.

Various herb extracts may be optionally contained in composition of the invention.Example is pomegranate, white birch (Betula Alba), green tea, camomile, Radix Glycyrrhizae and its extract combination.The extract can be carried in solvent be respectively hydrophily or Hydrophobic water-soluble or water-insoluble substance.Water and ethyl alcohol are preferred Extraction solvents.

Also may include material such as below: resveratrol, ellagic acid, kinetin, regards yellow oxygroup trimethyl at alpha-lipoic acid Silane (can be obtained with Silcare 1M-75 trade mark from Clariant Corp.), dehydrobenzene (DHEA) and their combination. Ceramide (including Cer EOS, Cer NP, Cer NP B, Cer AP and ceramide 7) and false manifestation of vitality are through acyl Amine can also be used for many compositions of the invention, but can also be excluded.The amount of these materials can 0.000001% to 10%, It is preferred that 0.0001% to 1% range.

Personal care composition can further include the film forming polymer of about 0.1 weight % to about 8 weight %.Such film forming Polymer include but is not limited to polyalkylene oxygroup sealing end polyamide (for example, INCI title: Polyamide-3, polyamide -4), Polyether-polyamide (for example, INCI title: polyamide -6), the polyamide for mixing acid blocked (for example, INCI title: polyamide -7) With poly- (ester-acid amide) (for example, the INCI title: polyamide -8) of ester sealing end.Such film forming polymer can synthesize or commercially available It arrives, such as with Sylvaclear^TMProduct line is purchased from Arizona Chemical Company, LLC and with OleoCraft^TMIt produces Strain column are purchased from Croda International PLC.Film forming polymer further includes but is not limited to the (example of polyester -5 of INCI name Such as, Eastman AQ^TM38S polymer), PPG-17/IPDI/DMPA copolymer is (for example, Avalure^TMUR 450 polymerize Object), acrylate copolymer is (for example, Avalure^TM120 polymer of AC) and polysaccharide such as Xilogel (tamarind gum (tamarin gum))), lotus flower bean gum, tara gum, beta glucan, short mould polysaccharide, carboxymethyl cellulose, the hydroxy propyl cellulose of waking up Element, mosanom, potato starch, carrageenan.Film forming polymer may include it is above-mentioned any two or more polymer combination. The amount of film forming polymer can be 0.1 weight % to 8 weight % in personal care composition.

Preservative can desirably prevent the growth of potentially harmful microorganism in composition incorporated herein.For this The suitable traditional preservatives of inventive composition are the Arrcostabs of P-hydroxybenzoic acid.The other preservative packets begun to use recently Include hydantoin derivatives, propionate and various quaternary ammonium compounds.Cosmetic chemistry man is familiar with preservative appropriate, and conventional Ground selects them to meet preservation challenge and test and provide product stability.Particularly preferred preservative is butylamino formic acid iodine For propine base ester, Phenoxyethanol, pungent glycol (caprylyl glycol), C_1-6P-hydroxybenzoate (especially para hydroxybenzene Methyl formate and/or propylparaben), imidazolidinyl urea, dehydroactic acid sodium and benzylalcohol.Preservative should be according to composition Purposes and preservative and lotion between other ingredients possible incompatibility select.Preservative preferably with 0.01% to 2% amount uses.Especially preferred combination is Octocrilene (octocrylene) and pungent glycol, because Xin Gan has been disclosed Alcohol enhances UVA and UVB protection.

The antifungal agent being suitably included in personal care composition is well-known to those skilled in the art.Example includes But be not limited to Climbazole, ketoconazole, Fluconazole, clotrimazole, Miconazole, econazole, etaconazole, Terbinafine, in these Any one or more salt (such as hydrochloride), zinc pyrithione, selenium disulfide and its two or more combination.

In some embodiments, personal care composition of the invention includes vitamin.Illustrative vitamin is dimension Raw element A (retinol), vitamin B2, vitamin B3 (niacin), vitamin B6, vitamin B12, vitamin C, vitamin D, dimension Raw element E, vitamin K and biotin.The derivative of vitamin also can be used.For example, vitamin C derivatives include four different palmitinic acids Acid ascorbyl ester, Ascorbic acid 2-phosphate magnesium and ascorbic acid glucoside.The derivative of vitamin E includes Tocopherol acetate ester, palm fibre Palmitic acid acid Renascin and tocopheryl linoleate.DL-panthenol and derivative also can be used.In some embodiments, vitamin B6 derivative is pyridoxine palmitate.Flavonoids, especially glucityl aurantiamarin, rutin sophorin and isoflavones also can be used (including genistein, Daidzein, equol and their glycosyl derivative) and their mixture.When it is present, The total amount of vitamin or flavonoids can 0.0001% to 10% or 0.001% to 10% or 0.01% to 10% or The range of person 0.1% to 10% or 1% to 10% or 0.01% to 1% or 0.1% to 0.5%.

In some embodiments, personal care composition of the invention includes enzyme, such as such as oxidizing ferment, protease, rouge Fat enzyme and their combination.In some embodiments, personal care composition of the invention include with Biocell SOD from The superoxide dismutase that Brooks Company (U.S.) is commercially available.

In some embodiments, personal care composition of the invention includes Desquamation promoters.In some embodiments In, personal care composition of the invention include 0.01% to 15% or 0.05% to 15% or 0.1% to 15% or The Desquamation promoters of 0.5% to 15% concentration of person.

Illustrative Desquamation promoters include monocarboxylic acid.Monocarboxylic acid can be carbon chain lengths be at most 16 substitution or do not take Generation.In some embodiments, carboxylic acid is alpha-hydroxy carboxylic acid compounds, beta-hydroxycarboxylic acids or polyhydroxycarboxyliacid acid.Term " acid " means not It only include free acid, but also including its salt and its C₁-C₃₀Arrcostab or aryl ester, and by going water removal with formed it is cyclic annular or Linear lactone structures and the lactone generated.Representative acid includes glycolic, lactic acid, malic acid and tartaric acid.In some implementations In scheme, salt is ammonium lactate.In some embodiments, beta-hydroxycarboxylic acids are salicylic acids.In some embodiments, phenolic acid packet Include ferulic acid, salicylic acid, kojic acid and their salt.

In some embodiments, at least one other component can based on the weight of composition 0.000001% to 10% or 0.00001% to 10% or 0.0001% to 10% or 0.001% to 10% or 0.01% to 10% or 0.1% to 10% or 0.0001% to 1% exists.Colorant, opacifier or grinding agent can also reside in this In the composition of invention.Colorant, opacifier or grinding agent can based on the weight of composition 0.05% to 5% or 0.1% To 3% concentration by comprising.

In some embodiments, personal care product of the invention also may include peptide, the pentapeptide being such as example commercially available Derivative-Matrixyl^TM, can be commercially available from Sederma, France.In another example, in some embodiments, Personal care product of the invention also may include carnosine.

Composition of the invention may include other optional components of wide scope.CTFA Cosmetic Ingredient Handbook (second edition, 1992) (entire contents are herein incorporated by reference) is described suitable for the present composition Commonly used in the various unrestricted cosmetics and drug ingedient in topical cosmetic skin care industry.Example includes: Antioxidant, binder, bio-additive, buffer, colorant, thickener, polymer, astringent, aromatic, wetting agent, Opacifier, conditioner, exfoliant, pH adjusting agent, preservative, natural extract, essential oil, skin sensing object (skin Sensate), Skin Soothing Agent and skin healing agent.

The form of composition

Composition of the invention is preferably non-solid.The preferred leave-on composition of composition of the invention.Combination of the invention Object preferably applies to stop leave-on composition on the skin.These leave-on compositions should be applied to skin and then exist It is distinguished after product application or by the composition that washing, flushing, wiping etc. are removed during application.Commonly used in washing away The surfactant of type (rinse-off) composition has the foam/fertilizer for allowing them to generate when in use and being easy to rinse The physicochemical properties of soap bubble (lather)；They can be made of anion, cation, both sexes and non-ionic mixture. On the other hand, do not need that there is such property for the surfactant in leave-on composition.More precisely, due to leave Composition is not intended to rinse out, they need to be nonirritating, it is therefore desirable to surfactant in leave-on composition The total content of total content and anionic surfactant minimizes.The total content of surfactant is preferred in the present composition 1% to no more than 10%, more preferably less than 8%, most preferably up to 5%, most preferably at most 3%.

In some embodiments, anionic surfactant is present in leave skin care compositions and methods with following amount In: with the poidometer 0.01% of composition to most 5%, perhaps with the poidometer 0.01% to 4% of composition or with combination The poidometer 0.01% to 3% of object perhaps (is less than with the poidometer 0.01% to 2% of composition or be substantially absent 1%, or less than 0.1%, or less than 0.01%).In some embodiments, in skin care compositions and methods surfactant it is total Content is no more than 10%, is perhaps lower than 8% or at most 5%.

In some embodiments, surfactant is selected from by anionic active object, non-ionic activity object, cation Type active matter and amphiprotic activity object.

In some embodiments, nonionic surface active agent be have it is those of following: C₁₀-C₂₀Fatty alcohol is hydrophobic Object or fatty acid hydrophobe are condensed with every mole of 2 to 100 mole ethylene oxide of hydrophobe or propylene oxide；With 2 to 20 moles The C of alkylene oxide condensation₂-C₁₀Alkyl phenol；Ethylene glycol fatty acid ester and di-fatty acid esters；Fatty mono glyceride；It loses Water D-sorbite list C₈-C₂₀Two C of fatty acid and anhydrosorbitol₈-C₂₀Fatty acid；With polyoxyethylene sorbitan and A combination thereof.In some embodiments, nonionic surface active agent is in the following group: alkyl poly glucoside, sugared fatty acid amide (such as methyl glucose amide) and trialkylamine oxides.

In the skin care compositions and methods of some embodiments according to the present invention, suitable amphoteric surfactant includes Cocoamidopropyl, C₁₂-C₂₀The double both sexes base second of trialkyl betaines, Sodium Lauroamphoacetate and lauroyl Sour sodium.

In the skin care compositions and methods of some embodiments according to the present invention, suitable anionic surfactant Including soap, alkyl ether sulfate and alkylether sulfonate, alkyl sulfate and alkylsulfonate, alkylbenzene sulfonate, alkyl sulphur Base succinate and dialkyl sulfosuccinates, C₈-C₂₀Acyl isethinate, C₈-C₂₀Alkyl ether phosphate, C₈-C₂₀Flesh Propylhomoserin salt, C₈-C₂₀Acyl-lactate, sulfosalicylic acetate and their combination.

Composition of the invention is usually in the emulsion form that can be oil-in-water or Water-In-Oil.In some embodiments, Personal care composition is toilet cream and creme or emulsion based on oil-in-water emulsion.Toilet cream matrix includes 5% to 40% Fatty acid and 0.1% to 20% soap.In such creme, fatty acid is preferably essentially the mixing of stearic acid and palmitinic acid Object, and the sylvite of the preferably described fatty acid mixt of soap, although the mixture of other counter ion counterionsl gegenions and they can be used.Snowflake Fatty acid in cream base matter is commonly using the mixture that substantially (normally about 90% to 95%) is stearic acid and palmitinic acid It is prepared by hystric acid.Typical hystric acid include the about 52-55% of total palmitinic acid-stearic acid mixture palmitinic acid and 45-48% stearic acid.Therefore, comprising hystric acid and its soap to prepare toilet cream matrix within the scope of the invention.It is especially excellent Selecting the composition includes higher than 7%, preferably higher than 10%, more preferably higher than 12% fatty acid.Typical toilet cream matrix By crystalline network structuring, and it is sensitive to the addition of various composition.

In one embodiment, personal care composition is formulated as with the cystine being substantially dissolved in water phase Water-in-oil emulsion.In one embodiment, personal care composition is formulated as water in oil emulsion of the cystine in aqueous drop Liquid, wherein at least 90% drop have 100 nanometers to 20 microns or selectively 200 nanometers to 20 microns or to 10 microns Diameter in range.

In some embodiments, other than containing skin lightening additive, also personal care composition is formulated as Facial mask.In some embodiments, other than containing skin lightening additive, also according in U.S. Patent No. 5139771 Personal care composition is formulated as facial mask by the formula.In some embodiments, in addition to containing skin lightening additive Except, personal care composition is formulated as facial mask also according to formula described in U.S. Patent No. 4933177.In some realities It applies in scheme, in addition to containing other than GSH precursor, also according to formula described in U.S. Patent No. 6001367 by personal nursing Composition is formulated as facial mask.

In some embodiments, other than containing skin lightening additive, also personal care composition is formulated as Shampoo.In some embodiments, personal care composition of the invention is formulated as deodorant.In some embodiments In, other than containing skin lightening additive, individual is protected also according to formula described in U.S. Patent No. 7,282,471 Reason composition is formulated as deodorant.In some embodiments, personal care composition of the invention is formulated as antiperspirant.? In some embodiments, other than containing skin lightening additive, described in U.S. Patent No. 7,282,471 Personal care composition is formulated as antiperspirant by formula.

In some embodiments, personal care composition of the invention is formulated as the personal nursing l Water Paper being intended for single use Towel product.In some embodiments, other than containing skin lightening additive, also according to U.S. Patent No. 7,282,471 Personal care composition is formulated as the personal nursing hygenic towelette product being intended for single use by the formula described in number.

In some embodiments, personal care composition of the invention is formulated as soap bar.In some embodiments, In addition to containing other than skin lightening additive, also according to formula described in U.S. Patent No. 7,282,471 by personal nursing Composition is formulated as soap bar.

The method for preparing skin care compositions and methods

In some embodiments, skin care compositions and methods according to the present invention can be prepared in the following manner:

A. all water soluble ingredients (including preservative, thickening polymer, the glycerol being optionally present) and water are mixed；

B., the mixture is heated to 70-90 DEG C of temperature；

C. all oil-soluble ingredients and formula (1) compound are mixed to 70-90 DEG C of temperature；

D. mixed oil-soluble ingredients are added in the mixture of water soluble ingredient heating, and mixed by agitation It closes, mixture is maintained to 70-90 DEG C of temperature；With

E. mixture is cooled to room temperature while mixing.

In some embodiments, personal care composition of the invention is prepared by the way that lotion is made.

A. by cystine it is expected that content is dissolved in high pH (9 to 14 or 9 to 12) aqueous solution,

B. the thick lotion in oil is prepared with the solution and emulsifier, then,

C. acidic aqueous solution is added under mixing, obtains lotion of the pH in the neutral range needed for topical composition, most Afterwards,

D. so that the lotion is subjected to high shear or is homogenized or sound spectrum processing (sonolation) step, such as pass through homogeneous Device, such as the Nano DeBee homogenizer of BEE International (Massachusetts, USA) or by Sonic Sonolator (Sonolator) homogenizer of Corporation (Connecticut, USA) manufacture carries out, to generate neutrality The uniform final lotion of pH range is more than the diameter of 90% drop in 100 nanometers to 20 microns of size range.

Use the method for skin care compositions and methods

In some embodiments, skin care compositions and methods are locally applied to application on human skin.In some embodiments, institute State skin care compositions and methods provide it is at least one selected from the benefit in the following group: skin condition, skin are smooth, reduce corrugation or old The skin of change reduces scytitis, reduces dry, reduction senile plaque, reduction sunburn and blast skin.

In some embodiments, by a small amount of skin care compositions and methods, such as 1 to 5ml, from suitable container or applicator It is applied to the exposed region of skin, and if desired, is then spread in skin using hand or finger or suitable device Above and/or wipe into skin.

Referring now to following embodiment, illustrated the present invention together with above description with non-limiting example some Embodiment.

Specific embodiment

Embodiment

Experimental method

The powder of following amino acid (glutamine and glycine) is purchased from Sigma, and by rebuilding in water (pH 7) The powder prepares the single mother liquor for carrying out every kind of amino acid.It is female that cystine (Sigma) is generated in 0.5M sodium hydroxide (pH 12) Liquid, because cystine is insoluble in neutral solution.As cystine ester l-cysteine di tert butyl carbonate dihydrochloride (DTBC) and L-cysteine diethylester dihydrochloride (DEC) is purchased from Bachem；L-cysteine dimethyl ester dihydrochloride (CDME) comes from Sigma. In order to generate the described herein after mixture for GAP, by three kinds of amino acid (glutamine, cystine and glycine) of proper volume Merge in Han Keshi balanced salt solution (Hank's Balanced Salt Solution) (Sigma), so that glutamine, The weight ratio of cystine and glycine is 0.5:1:1.Specific concentration used in each measurement (assay) see below.

Other test agent: 12- hydroxy stearic acid (Biotor Industries Pvt Ltd) is usually dissolved in second In alcohol or dimethyl sulfoxide.In following measurement, in appropriate circumstances, solvent is added in intermedium control sample, with Potential solvent effect is normalized.

Melanin content measurement

Making one primary melanocyte, (Cascade Biologics is now having for ThermoFisher Scientific) There is the melanin of human melanoma cell growth replenishers (two kinds of nutrient media components from ThermoFisher Scientific) Growth in cell growth medium (MGM).By melanocyte with 5 × 10⁴A cells/well is seeded in 24 orifice plates, and is being added In 37 DEG C and 5%CO in wet incubate box₂It is incubated under atmosphere.Incubate 24 hours after, with alone or in combination GAP amino acid or 12- hydroxy stearic acid handles cell culture.Intermedium control is by with medium GAP (0.002mMNaOH) and/or other survey The cell composition of agent medium of having a try processing.After treatment, by cell again in humidification incubate box in 37 DEG C and 5%CO₂Gas It is incubated 72 hours under atmosphere.At the end of 72 hours incubations, with 120 μ L/ hole melanin contents measurement reagent (in 1M sodium hydroxide Culture medium 10%DMSO) is replaced, and is incubated 1 hour at 60 DEG C in the incubate box of oscillation.Then supernatant is transferred to 384 Orifice plate.The absorbance of 405 nanometers is measured using microplate (GEnios Pro, Tecan) by spectrophotometric analysis.

Untreated cell (inactive) is considered as 100% melanin content in the spectrophotometric optical density of 405 nanometers. Utilize the relative black cellulose content of the normalization calculation processing sample based on untreated (culture medium/medium) control.

Glutathione measurement

By Human keratinocytes (Promocell, Heidelberg, Germany) have contain 5%CO₂Atmosphere Humidification incubate box in be maintained at 37 DEG C containing 60 μM of calcium chloride and 1% Human keratinocytes growth replenishers (come from Two kinds of nutrient media components of ThermoFisher Scientific)In culture medium.The culture of update in every 2-3 days Base.Then, cell is paved with carry out trypsin digestion with 90%, and with every hole 1 × 10⁴A density is seeded to white wall In 96 orifice plates of clear bottom.One day or two days after inoculation, cell culture was replaced with Han Keshi balanced salt solution (HBSS) Base, and with individually or combined with other above-mentioned test agent GAP (or 0.12-0.240mM sodium hydroxide intermedium control, PH 7.5) or individually l-cysteine ester pre-processes keratinocyte 1-2 hours.It constitutes mixed for the GAP in the measurement The concentration for closing all amino acid of object is specified in tables of data, and is fully described in following abbreviated list.

With GAP alone or in combination or after other test agent pre-processes one hour or two hours, then with 25 μM of first A kind of naphthoquinones (Sigma-Aldrich) (known oxidative stress inducer) challenge keratinocyte.After 18-20 hours, It harvests cell and analyzes total glutathione content, the reagent using commercial reagent box (GSH-GSSG GLo Assay, Promega) Box is for detecting the fluorescence-based system with total glutathione in quantitative culture cell.In short, being gone after cell processing It is replaced 5 minutes at 20-25 DEG C except culture medium and with cell cracking agent；Note that all remaining steps also at 20-25 DEG C into Row.Next, luciferase generation reagent to be added in each hole and incubate 30 minutes.After this step, by fluorescein Detection reagent is added in each hole and incubates plate 15 minutes.Finally, then in 3 plate reader of FlexStation Shining for plate is read in (Molecular Devices).After standard curve interpolation glutathione concentrations, total gluathione is calculated Peptide content.Experiment condition usually at least to repeat to determine progress three times.Use single factor test ANOVA computational statistics conspicuousness.It is logical It crosses and calculates protection percentage in following equation using the glutathione content of the calculating from each experiment:

Active oxygen species (ROS) measurement

By Human keratinocytes (Promocell, Heidelberg, Germany) have contain 5%CO₂Atmosphere It is maintained at 37 DEG C in humidification incubate box and grows replenishers (HKGS) containing 60 μM of calcium chloride and 1% Human keratinocytesIn keratinocyte culture medium.Every other day update culture medium.Then, cell is paved with carry out pancreas with 90% Protease digestion, and with every hole 1-2 × 10⁴A density is seeded in 96 orifice plates with black wall and clear bottom.It is being inoculated with Afterwards second day, with or without menadione (10-25 μM), GAP, GAP medium (0.2mM NaOH, pH 7.5), above-mentioned The combination of other test agent or GAP with other test agent or the Han Keshi balance salt of individual l-cysteine ester are molten Liquid (HBSS) replaces cell culture medium, and incubates again 18 hours.For ROS detect, by CellROX it is green (Life Tech, Thermo Fisher Scientific, Rockford, USA) reagent is added to the ultimate density of each Kong Zhongzhi 15-25 μM, And it is incubated again at 37 DEG C 2-4 hours in humidification incubate box.It uses Tecan microplate (excitation/emission=490/525) Detect ROS fluorescence.Opposite ROS is calculated using the normalization handled based on the intermedium control for being set as 100% to generate.It is pointing out In the case where, the Relative fluorescence units in following equation using measurement calculate protection percentage, individually locate as with menadione The comparison of reason:

ROS content is evaluated together with cell viability, because if processing toxicity is so big, so that making in measurement Cell death (and there is no any detectable ROS), then may obtain the false negative of ROS.If cell is still survived, The reduction of ROS content is meaningful.

Cell viability measurement

Human keratinocytes (Promocell, Heidelberg, Germany) are maintained at containing 60 μM of calcium chloride and 1% Human keratinocytes grow replenishers (HKGS's)In keratinocyte culture medium.Every other day update Culture medium.Then, cell is paved with carry out trypsin digestion with 90%, and with every hole 2 × 10⁴A density is seeded to 96 holes In hyaline tissue's culture plate.Second day after inoculation, cell culture was replaced with the processing as described in ROS above measurement part Base.After 18 hours, by cell culture kit -8 (CCK-8) reagent (Dojindo, Kumamoto, Japan) in HBSS with 1:10 dilution, and incubated together with cell at 37 DEG C 4 hours in the incubate box of humidification.It is read using Tecan Safire2 plate Number device measures the light absorption of 450 nanometers.It is calculated using the normalization compareed based on the carrier intermediate for being set as 100% opposite Vigor.

In the case where pointing out, the relative absorbance units in following equation using measurement calculate protection percentage, make For compared with menadione is individually handled:

Abbreviation in embodiment is as follows:

MM=mMs

μM=micromole

μ L=microlitre

GAP=glutamine (32 μM), cystine (40 μM), glycine (129 μM)

HR=4- hexyl resorcin

The sodium pyroglutamate of GAP 10=8 μM, 10 μM of cystine, 32 μM of glycine

The sodium pyroglutamate of GAP 20=16 μM, 20 μM of cystine, 64 μM of glycine

The sodium pyroglutamate of GAP 60=48 μM, 60 μM of cystine, 192 μM of glycine

DEC=L- cystamine diethyl phthalate dihydrochloride

CDME=L- cystine dimethyl dihydrochloride

DTBC=L- cystine di tert butyl carbonate dihydrochloride

Embodiment 1

The skin lightening potentiality of the research present composition of embodiment 1.The result of acquisition is summarized in table 1A.Institute in table There is the weight % in number expression composition.

The inhibition of table 1A- B16 cell

Statistically significant improvement:

¹Compared with culture medium and intermedium control, p < 0.05

²Compared with individual GAP, p < 0.05

³Compared with individual 12- hydroxy stearic acid, p < 0.05

In table 1A, the sample marked by alphabetic character is except the scope of the present invention.The sample of numeral mark is at this In the range of invention.Sample C in table 1A is positive control, because it uses 4- hexyl resorcin, (known height has The skin lightening agent of effect).Generally speaking, from the result in table 1A can be seen that with using individual 12- hydroxy stearic acid or The result that GAP is obtained is compared, and PPAR activation fatty acid (12- hydroxy stearic acid) causes to cooperate with improvement with the combination of GAP amino acid (synthesis for inhibiting melanin).

Embodiment 2

Embodiment 2 generates the amino acid for having rated and constituting GSH and constructing module for intracellular GSH is enhanced.The result of acquisition It is summarized in table 2A.The effect of table 2B is into 2D, is also tested for various cystine esters.

Table 2A-glutathione synthesis

Statistically significant reduction:

¹Compared with HR+GAP10+ menadione, p < 0.05

Statistically significant improvement:

²Compared with intermedium control+menadione, p < 0.05

Table 2B-glutathione synthesis

Statistically significant reduction:

¹Compared with intermedium control, p < 0.05

Statistically significant improvement:

²Compared with intermedium control+menadione, p < 0.05

Table 2C-glutathione synthesis

Statistically significant reduction:

¹Compared with intermedium control, p < 0.05

Table 2D-glutathione synthesis

Statistically significant reduction:

¹Compared with intermedium control, p < 0.05

Statistically significant improvement:

²Compared with intermedium control+menadione, p < 0.05

Embodiment 3

Embodiment 3 is reduced for the improvement of oxygen species has rated the amino acid for constituting GSH building module.The result of acquisition is converged Always in table 3A into 3A.The effect of table 3B is also tested for various cystine esters into 3D.

The reduction of table 3A- oxygen species

Statistically-significant difference:

¹Compared with intermedium control, p < 0.05

Statistically-significant difference:

²Compared with intermedium control+menadione, p < 0.05

The reduction of table 3B-active oxygen species

Statistically-significant difference:

¹Compared with intermedium control, p < 0.05

Statistically-significant difference:

²Compared with intermedium control+menadione, p < 0.05

The reduction of table 3C- oxygen species

Statistically-significant difference:

¹Compared with intermedium control, p < 0.05

Statistically-significant difference:

²Compared with intermedium control+menadione, p < 0.05

The reduction of table 3D- oxygen species

Statistically-significant difference:

¹Compared with intermedium control, p < 0.05

Statistically-significant difference:

²Compared with intermedium control+menadione, p < 0.05

Embodiment 4

Personal nursing formulation according to the present invention is shown in following table.All numbers in table indicate the weight in composition Measure %.

Table I-oil-in-water formulation, emulsion and creme

Table II-Water-In-Oil topical cream or creme

Table III-toilet cream

Claims

1. a kind of local skin lightening composition, it includes:

A. skin lightening additive, the poidometer with the composition includes:

I. the cystine of about 0.001% to about 2%；

Ii. about 0.01 to about 10% selected from the glutamic acid Yanyuan in the following group: glutamine, glutamic acid, pyroglutamic acid and they Mixture；

Iii. the glycine of about 0.01% to about 10%；With

Iv. the PPAR of about 0.01% to about 5% activates fatty acid；With

B. acceptable carrier on cosmetics；

C. wherein the pH of the composition in the range of about 3.5 to about 8.5.

2. composition according to claim 1, wherein PPAR activates fatty acid in the following group: 12- hydroxy stearic acid, The cis- sub- oil of -12- conjugation of conjugated linoleic acid, ricinoleic acid, petroselic acid, cis- -9- anti-form-1 1- conjugated linoleic acid, anti-form-1 0- Acid, the trans- octadecanoid acid of 7-, cis--parinaric acid, docosahexaenoic acid, cis- -4,7,10,13,16,19- 22 Carbon acid, ricinelaidic acid, parinaric acid, octatecatrienoic acid, anti-linolenic acid, vaccenic acid, eicosapentaenoic acid, The mixture of Pinolenic acid and they.

3. composition according to any one of the preceding claims, wherein the glutamate source be pyroglutamic acid or its Salt.

4. composition according to any one of the preceding claims, wherein the PPAR activated acids are 12- hydroxy stearic acids.

5. composition according to any one of the preceding claims, wherein the PPAR activated acids are conjugated linoleic acid.

6. composition according to any one of the preceding claims, wherein the PPAR activated acids are petroselic acids.

7. composition according to any one of the preceding claims, wherein the composition is in include the cystine in water phase Water-in-oil emulsion form, wherein 90% water droplet has diameter in 100 nanometers to 20 microns of size range.

8. composition according to any one of the preceding claims, it includes the selenium sources of 0 to most 0.1%.

9. composition according to any one of the preceding claims, wherein the composition is the non-solid skin of leave Cosmetic composition.

10. composition according to any one of the preceding claims, wherein the composition is toilet cream.

11. composition according to any one of the preceding claims, wherein the composition further includes between 4- alkyl Benzenediol.

12. composition according to any one of the preceding claims, wherein the composition further includes niacinamide.

13. composition according to any one of the preceding claims, wherein total amino acid and PPAR activate the weight of fatty acid Ratio is measured in the range of 10:1 to 20:1.

14. improving the method for the appearance of skin comprising Xiang Suoshu skin applies according to any one of preceding claims Composition.

15. obtaining even skin tone and reducing pigmentation, senile plaque and the method for discoloration comprising Xiang Suoshu skin applies basis Composition described in any one of preceding claims.